Use of Liposomal Bupivacaine in the Postoperative Management of Posterior Spinal Decompression

Design

Retrospective cohort-matched chart review

N = 116

Objective

To evaluate the efficacy of long-acting liposomal bupivacaine in comparison with bupivacaine hydrochloride for lowering postoperative analgesic usage in the management of posterior cervical and lumbar decompression and fusion

Study Groups

Posterior cervical surgery (n = 52)

Posterior lumbar surgery (n = 64)

Inclusion Criteria

Age range 18–80 years, an American Society of Anesthesiologists Physical Status Classification of I to III, scheduled to undergo elective primary posterior decompression and fusion for spondylotic pathologies

Exclusion Criteria

Patients with previous surgical interventions at the same level or anterior approaches, patients with trauma/fractures/tumors, those who did not receive a fusion, and patients who experienced complications during hospitalization 

Methods

Liposomal bupivacaine was administered to all patients undergoing posterior-approach cervical and lumbar spinal surgery at the institution beginning on January 1, 2014. The protocol consisted of injecting 20 mL liposomal bupivacaine (1.3% concentration) into the paraspinal musculature at the operative levels prior to wound closure, rather than 20 ml of 0.5% bupivacaine hydrochloride, which was used from October 2013 to January 1, 2014. As part of the multimodal pain protocol, all patients received preemptive patient-controlled anesthesia (PCA) and oral pain medications postoperatively as well. Patients who were receiving chronic narcotics preoperatively were maintained on the same regimen during their hospitalization.

Duration

October 2013 to February 2015

Outcome Measures

Analgesic requirements, length of stay

Baseline Characteristics

Cervical Cohort

Lumbar Cohort 

Bupivacaine HCl

Liposomal Bupivacaine

Bupivacaine HCl

Liposomal Bupivacaine 

Age, years

Female

Mean BMI, kg/m²

Chronic narcotics

Mean PCA, days

Hospital length of stay

Periop complications *

Includes wound infection within 30 days (4 occurrences), dural tear (3 occurrences), postoperative fever (2 occurrences), altered mental status (2 occurrences), dysphagia (2 occurrences), hypotension (2 occurrences), 24-hour return (1 occurrence), chronic obstructive pulmonary disease exacerbation (1 occurrence), fall (1 occurrence), ileus (1 occurrence) proximal weakness (1 occurrence), sickle-cell crisis (1 occurrence), urinary tract infection (1 occurrence), and wound dehiscence (1 occurrence).

Cervical Cohort (n = 52)

Lumbar Cohort (n = 64)

Results

Endpoint

Bupivacaine HCl

Liposomal Bupivacaine

P-value

Narcotic Use, MME

Intravenous rescue pain medicine, MME

Opiate-Naive

No. of patients

Preop narcotic use, MME/day

Postop narcotic use, MME/day

Postop narcotic use, MME/day/operative level

24

0

12.0

2.3

14

0

13.7

2.5

0.68

--

0.70

0.86

23

0

16.6

4.9

22

0

18.2

6.2

0.91

--

0.84

0.59

Opiate-Tolerant

No. of patients

Preop narcotic use, MME/day

Postop narcotic use, MME/day

Postop narcotic use, MME/day/operative level

7

2.8

83.4

17.3

7

1.5

18.3

3.2

0.41

0.18

0.22

0.24

11

1.8

130.7

43.2

8

3.0

26.5

8.8

0.75

0.21

0.25

0.26

Length of Stay

Abbreviations: MME, morphine milligram equivalent; PCA, patient-controlled anesthesia

Adverse Events

The most common complications encountered were dural tears, dysphagia, hypotension, postoperative fever, and post-discharge infection. The infection and complication rates between cohorts and treatment arms were not significantly different between cohorts or treatments.

Study Author Conclusions

Liposomal bupivacaine did not appear to significantly decrease perioperative narcotic use or length of hospitalization, although there was a trend toward decreased narcotic use in comparison with bupivacaine hydrochloride. While the results of this study do not support the routine use of liposomal bupivacaine, there may be a benefit in the subgroup of patients who are chronic opiate users. Future prospective randomized controlled trials, ideally with dose-response parameters, must be performed to fully explore the efficacy of liposomal bupivacaine, as the prior literature suggests that clinically relevant effects require a minimum tissue concentration.

InpharmD Researcher Critique

The study lacked direct patient-reported pain scores, relying on medication use as a proxy. Its small sample size raised the risk of Type 2 errors, especially among chronic opioid users. Variability in pain medication delivery methods and missing data on medication quantities introduced potential bias. The study's unique drug comparison, focusing on pharmacokinetics, makes direct comparisons with prior research challenging. Furthermore, while it noted differences in analgesic use, it found no significant impact on length of stay or complications, highlighting the complexity of postoperative outcomes.

The Efficacy of Liposomal Bupivacaine in Lumbar Spine Surgery

Design

Prospective randomized single-blinded control trial; N= 50 

Objective

To determine if the local anesthetic liposomal bupivacaine (LB) reduces the total opioid requirement in the first 3 days following posterior lumbar decompression and fusion (PLDF) surgery for degenerative spondylosis

Study Groups

Liposomal bupivacaine Group (n= 24)

Control Group (n= 26)

Inclusion Criteria

Aged ≥18 years, undergoing a primary elective, open posterior lumbar decompression and instrumented fusion surgery for degenerative spondylosis 

Exclusion Criteria

Active infection, primary or metastatic malignancy of the spine, fracture of a lumbar vertebra, history of narcotic or other substance abuse, impaired cardiovascular function

Methods

Procedures were performed by 4 fellowship-trained orthopedic spine surgeons. Patients were randomized (1:1) to receive 266 mg of LB in a 60-mL suspension or 60 mL of 0.9% sterile saline (placebo group). Local injections were made prior to wound closure. Research staff and investigators administering the injections were not blinded to patient group assignments, as the appearance of LB suspension was noticeably different from that of placebo. 

All patients had a patient-controlled analgesia (PCA) pump that began shortly after surgery and was discontinued at 0600 on postoperative day 1. Intravenous (IV) and PO opioid pain medications were used only as necessary for adequate control. For further subgroup analysis, patients were identified to be either narcotic tolerant (NT) or narcotic naive (NN). Those taking opioids before the time of surgery were considered NT. At the end of the 72-hour postoperative period, the dosages in mg for PCA, IV, and PO opioid analgesics consumed by each patient were normalized to 10 mg IV morphine of 1 mg morphine milligram equivalent (MME). 

Duration

Enrollment: August 2015 to October 2016

Follow-up: 72 hours postoperatively 

Outcome Measures

Primary outcome: total 72-hour postoperative opioid consumption between the treatment and control group

Secondary outcome: visual analog scale (VAS) pain scores and hospital length of stay

Baseline Characteristics

LB Group (n= 24)

Control Group (n= 26)

Age, years

Female

Mean body mass index, kg/m²

Active smoker

Surgical characteristics

No. of vertebrae decompressed

No. of vertebrae instrumented

Operation length, min

Estimated blood loss, mL

3.5 ± 0.98

2.3 ± 0.5

174.± 6 59.8

369.6 ± 154.1

3.7 ± 0.18

2.5 ± 0.6

168.7 ± 56.3

451.0 ± 262.5

No significant differences were noted in baseline characteristics between the two study groups.  

Results

Endpoint

LB Group (n= 24)

Control Group (n= 26)

p-value

72-hour postoperative MME

PCA

IV

PO

Total

4.5 ± 3.6

1.3 ± 1.4

5.9 ± 5.7

11.6 ± 9.3

5.1 ± 4.5

1.2  ± 1.0

7.1  ± 5.4

13.4 ± 8.9 

0.79

0.83

0.35

0.40

VAS Scores 

Preoperative 

Postoperative days 1-3 

5.8 ± 3.2

5.0 ± 2.7

4.4 ± 3.3

4.8 ± 2.8

0.13

0.80

Hospital length of stay, days

Total MME

NT

NN  

13.3 ± 12.2 (n= 11)

10.2 ± 6.0 (n= 13) 

20.6 ± 9.3 (n= 9)

9.6 ± 6.1 (n= 17)

0.048

0.72

Adverse Events

Study Author Conclusions

In the setting of PLDF surgery, LB injections did not significantly reduce the consumption of opioids in the first 3 postoperative days, nor did the hospital length of stay or VAS pain scores, compared to saline. However, LB could be beneficial in reducing the consumption of opioids in narcotic-tolerant populations.

InpharmD Researcher Critique

Opioid-based analgesics are often associated with a high number of adverse events, yet this article did not disclose adverse events experienced by patients in the treatment group. Generalizability of study findings is limited by the small sample size and patients undergoing PLDF surgeries only. 

Can Liposomal Bupivacaine Be Safely Utilized In Elective Spine Surgery?

Design

Single-blinded, prospective, randomized controlled trial

N= 59

Objective

To compare the incidence of adverse events (AEs) and hospital length of stay between patients who received liposomal bupivacaine (LB) versus a single saline injection following posterior lumbar decompression and fusion surgery for degenerative spondylosis 

Study Groups

LB (n= 33)

Placebo (n= 26) 

Inclusion Criteria

Age ≥ 18 years, undergoing a primary 1- or 2-level elective open posterior lumbar decompression and instrumented fusion for degenerative spondylosis, had any number of laminectomies, a 1- or 2-level fusion, with at least 1 level involving lumbar vertebrae. 

Exclusion Criteria

Methods

Patients were randomized (1:1) to receive either 60 mL injection of 266 mg LB or 60 mL of 0.9% sterile saline. Local injections were made prior to wound closure into the exposed paraspinal muscles and surrounding soft tissues. All patients had a patient-controlled analgesia pump initiated shortly after surgery that was discontinued at 6 AM on postoperative day 1. Intravenous and oral opioid-based pain medications were used as necessary for adequate pain control throughout the postoperative period in conjunction with other nonopioid medications.

Duration

Enrollment: August 2015 to October 2016

Evaluation: 72 hours after surgery

Outcome Measures

Primary: incidence of postoperative AEs

Baseline Characteristics

LB (n=33)

Placebo (n=26)

Age, years

Male:Female, 

Body mass index, kg/m²

Charlson comorbidity index score

Length of stay, days

Results

Adverse Events

LB (n=33)

Placebo (n=26)

p-value

Nausea

Vomiting

Constipation

Urinary retention

Hypotension

Arrhythmias

Pruritus

Headache

Acute mountain sickness

Acute respiratory distress

Desaturation

Pyrexia

Adverse Events

See results

Study Author Conclusions

In this prospective randomized pilot study of 59 patients who underwent posterior laminectomy and instrumented spinal fusion surgery, single-dose injections of LB into the surgical site prior to wound closure did not significantly increase or decrease the incidence and risk of developing AEs in the immediate postoperative period, nor had any significant effect on the hospital length of stay. To better assess the safety profile of LB in spine surgery, carefully designed studies involving a larger sample size are warranted.

InpharmD Researcher Critique

This study was limited to safety evaluations. Conclusions regarding the efficacy of LB in spinal surgery cannot be made based on this study.

Efficacy of liposomal bupivacaine in pediatric patients undergoing spine surgery

Design

Single-center, retrospective matched cohort study

N= 141

Objective

To evaluate the use of liposomal bupivacaine in a cohort of pediatric patients undergoing multisegment spinal surgery to determine whether the use of liposomal bupivacaine reduces the amount of 72-hour postoperative opioid or other analgesic use

Study Groups

Control (n= 94)

Liposomal bupivacaine (n= 47)

Inclusion Criteria

Pediatric patients, underwent a surgical procedure involving posterior spinal fusion performed by a single surgeon at a single institution

Exclusion Criteria

Methods

Patients were identified via the hospital's electronic medical record. Patients who received liposomal bupivacaine were matched 1:2 with patients who received plain bupivacaine (control) on type and extent of surgery and then on age and gender within 3 years. Postoperative pain management was at the discretion of the treating physician and, in general, included intravenous (IV) opioids administered by patient-controlled analgesia immediately post-operation, followed by a transition to oral opioid medication when tolerated. IV acetaminophen (APAP) and IV ketorolac were used either scheduled or as needed for breakthrough pain.

Duration

Surgery: February 2011 to May 2016

Data collection: up to 72 hours after procedure

Outcome Measures

Primary: difference in total amount of IV morphine equivalents per kg of weight used in postoperative period

Secondary: total amount of IV APAP per kg of weight and total IV ketorolac per kg of weight administered during postoperative period

Baseline Characteristics

Control (n= 94)

Liposomal bupivacaine (n= 47)

Age, years (range)

Male

Number of spinal segments fused

11-15

> 15

91

3

45

2

Results

Endpoint

Control (n= 94)

Liposomal bupivacaine (n= 47)

95% confidence interval

p-value

Morphine equivalents, mg/kg

IV APAP, mg/kg

IV ketorolac, mg/kg

Adverse Events

Common Adverse Events: Not disclosed

Serious Adverse Events: Not disclosed

Percentage that Discontinued due to Adverse Events: N/A

Study Author Conclusions

Liposomal bupivacaine was not associated with reductions in postoperative opioid use in pediatric spinal surgery.

InpharmD Researcher Critique

This study is likely limited by confounding variables, including treatment bias, due to patients not being blinded to their treatment group.

Enhanced Recovery After Surgery Protocol for Lumbar Spinal Surgery With Regional Anesthesia: A Retrospective Review

Design

Retrospective review

N= 24

Objective

To analyze the efficacy of the enhanced recovery after surgery (ERAS) protocol with intraoperative modified thoracolumbar interfascial plane (mTLIP) block to determine whether these interventions reduce the length of stay (LOS) and opioid requirements during the postoperative period

Study Groups

Pre-ERAS (n= 12)

Post-ERAS (n= 12)

Inclusion Criteria

Exclusion Criteria

Admitted for trauma, required dialysis, refused to receive regional anesthesia, pregnant

Methods

Outcomes before and after the implementation of the ERAS protocol were evaluated. The ERAS protocol consisted of preoperative administration of acetaminophen 1 g PO and gabapentin 300 mg PO. Intraoperative care included standard induction and maintenance, dexamethasone 8 mg, ketorolac 15 mg IV, ketamine 0.2 mg/kg IV bolus followed by 0.1 mg/kg/hour infusion, tranexamic acid (10 mg/kg loading dose followed by 1 mg/kg/hour infusion), and modified thoracolumbar interfascial plane block with 20 mL liposomal bupivacaine. Postoperative care included administration of various pain medications (acetaminophen, ketorolac, gabapentin, oxycodone, and hydromorphone), methocarbamol, and ketamine infusion.

Duration

Surgical period pre-ERAS protocol: January 1, 2017, to August 31, 2018

Surgical period post-ERAS protocol: September 1, 2018, to November 30, 2019

Outcome Measures

LOS, opioid equivalent requirement

Baseline Characteristics

Pre-ERAS (n= 12)

Post-ERAS (n= 12)

Age, years

There were reported to be similar distributions of men and women in both the pre- and post-ERAS groups, but specific data were not given.

Results

Endpoint

Post-ERAS (n= 12)

p-value

LOS, days

Opioid equivalent requirement, morphine milligram equivalents

Adverse Events

Common Adverse Events: Not disclosed

Serious Adverse Events: Not disclosed

Percentage that Discontinued due to Adverse Events: N/A

Study Author Conclusions

In patients treated with the ERAS protocol undergoing lumbar spinal surgery with the use of regional anesthesia via the mTLIP, we observed a statistically significant reduction in opioid administration and LOS for laminectomies. 

InpharmD Researcher Critique

This study is limited by its small sample size and retrospective design, which allows for certain biases and confounding factors. Additionally, regional anesthesia with bupivacaine was used in conjunction with multiple other treatments, limiting conclusions regarding the individual efficacy of liposomal bupivacaine.

Comparison of Bupivacaine Plus Magnesium Sulfate and Ropivacaine Plus Magnesium Sulfate Infiltration for Postoperative Analgesia in Patients Undergoing Lumbar Laminectomy: A Randomized Double-blinded Study

Design

Randomized, prospective, double-blind, comparative pilot study

N= 60

Objective

Study Groups

Bupivacaine with magnesium sulfate (group BM; n= 30)

Ropivacaine with magnesium sulfate (group RM; n= 30)

Inclusion Criteria

Exclusion Criteria

Methods

Patients were randomized to receive either 50 mg of bupivacaine combined with 500 mg of magnesium sulfate (1 mL) made up to 20 mL solution using normal saline (NS) or 50 mg of ropivacaine (10 mL) combined with 500 mg of magnesium sulfate (1 mL) made up to 20 mL solution using NS. The investigational agent was administered 30 minutes prior to skin closure. All patients received the same premedication and anesthesia strategy. Pain was measured via a Visual Analog Scale (VAS) from 1 to 10.

Duration

Outcome Measures

Baseline Characteristics

Group BM (n= 30)

Group RM (n= 31)

Age, years

Female

Body mass index, kg/m²

Duration of surgery, min

One patient from Group RM was excluded in the analysis of the results but included in the baseline presentation

Results

Endpoint

Group BM (n= 30)

Group RM (n= 30)

p-Value

Data was primarily presented as a graph. VAS scores were higher in group RM versus group BM at the 4th, 5th, 6th, and 8th hour.

Duration of postoperative analgesia, hours

7.3 ± 0.46

6.6 ± 0.69

0.0001

Nalbuphine consumption, mg

12 ± 4.07

15.33 ± 5.07

0.0068

Adverse Events

Postoperative urinary retention was the most common complication. Higher mean blood pressure was observed in both groups at the 7th and 8th hour. Peak heart rate was observed at the 6th and 7th hour in group BM and 7th and 8th hour in group RM.

Study Author Conclusions

InpharmD Researcher Critique

Clinical and Economic Outcomes Associated With Use of Liposomal Bupivacaine Versus Standard of Care for Management of Postsurgical Pain in Pediatric Patients Undergoing Spine Surgery

Design

Retrospective cohort

N= 10,189

Objective

To examine the association of opioid-related and economic outcomes with postsurgical liposomal bupivacaine (LB) or non-LB analgesia in pediatric patients who received spine surgery

Study Groups

LB (n= 373)

Non-LB (n= 9,816)

Inclusion Criteria

Age 1-17 years who underwent inpatient primary spine surgery (including discectomy, lumbosacral fusion, other fusion, laminectomy, or other spine surgery); received either LB analgesia or did not receive LB analgesia for pain management following the procedure

Exclusion Criteria

Multiple records of the same primary surgery admission; if hospital costs were ≥ 3 standard deviations beyond the mean cost (considered outliers)

Methods

A retrospective analysis of the deidentified Premier Healthcare Database that contains administrative data from > 1,000 US hospitals and health-care systems was performed to identify patients who met inclusion criteria using International Classification of Diseases (ICD)-9 and ICD-10 codes. 

Inpatient opioid prescription was extracted from standard charge master codes for opioids and converted into total morphine milligram equivalents (MMEs). Opioid-related adverse events (ORAEs) included cardiovascular, central nervous system, gastrointestinal, respiratory, skin, and other complications. 

Duration

January 1, 2015 to September 30, 2019

Follow up: entire hospitalization period from admission to discharge

Outcome Measures

Primary: inpatient opioid prescription 

Secondary: length of stay (LOS), total cost of hospital care, ORAEs

Baseline Characteristics

LB (n= 373)

Non-LB (n= 9,816)

Age, years

Female

White

Quan-Charlson Comorbidity Index

0-1

> 1

92.2%

7.8%

82.3%

17.7%

Index surgery year

2015

2016

2017

2018

2019

16.1%

26.8%

21.2%

14.7%

21.2%

21.8%

25.5%

23.2%

16.8%

12.7%

PCA

Spine surgery type

Discectomy

Fusion (lumbosacral)

Fusion (other)

Laminectomy

Other

1.6%

11.3%

67.8%

1.1%

18.2%

1.7%

5.8%

51.1%

1.7%

39.7%

PCA, patient-controlled analgesia

Results

Endpoint

LB (n= 373)

Non-LB (n= 9,816)

Adjusted Rate Ratio (95% confidence interval [CI]); p-Value

In-hospital postsurgical opioid consumption, MMEs

Patients with ORAEs

LOS, days

Total hospital costs, US dollars

8% lower total costs with LB; cost savings mostly attributed to hospital stay cost by room and board ($6,312 vs. 7,395; 15% savings) and central supply cost ($8,267 vs. 9,370; 12% savings)

Adverse Events

See results section. 

Study Author Conclusions

Pediatric patients undergoing spine surgery who received LB had significantly reduced in-hospital postsurgical opioid consumption, LOS, and hospital costs compared with those who did not. 

InpharmD Researcher Critique

This study is limited by its retrospective design introducing the risk for selection bias, as well as the relatively small population in the LB group compared to the non-LB group. Data was pulled from an administrative database, so clinical information was limited including baseline opioid intake which may have affected the primary outcome results.  

Does Local Administration of Liposomal Bupivacaine Reduce Pain and Narcotic Consumption in Adult Spinal Deformity Surgery?

Design

Retrospective cohort study

N= 159

Objective

To determine if local administration of liposomal bupivacaine (LB) reduces postoperative pain scores and narcotic use in spinal deformity patients 

Study Groups

Group L (received LB) (n= 90)

Group C (historical cohort who received bupivacaine alone) (n= 69)

Inclusion Criteria

Age > 18 years; undergoing either elective primary or revision long instrumented fusion (≥ 7 levels)

Exclusion Criteria

Tumor, infection, and trauma cases

Methods

The study was conducted within a single surgeon's clinical practice, with a historical comparative group. All patients underwent deformity correction under general anesthesia. Both groups, prior to incision, received periincisional 30 mL of 0.5% bupivacaine with epinephrine (5 mg/mL). For the LB cohort, at the conclusion of the case patients received 20 mL of LB (266 mg) diluted to 120 cc with normal saline into both the paraspinal musculature and subcutaneous tissue, bilaterally, along their entire lengths using an 18-gauge spinal needle. The historical cohort received 30 mL of 0.5% bupivacaine using a similar distribution technique. 

All patients were admitted to the hospital and started physical therapy on day 1 after surgery. Standard postoperative pain regimen included initial patient-controlled anesthesia with 0.2 mg hydromorphone every 8 min with an additional every 1 hour nurse directed bolus of 0.4 mg as needed for breakthrough pain. Additional medications included acetaminophen 650 mg PO every 4 hours, oxycodone 5 mg PO 1 to 2 tablets every 4 hours, cyclobenzaprine 5 mg PO every 8 hours, or diazepam 5 mg PO every 8 hours. Additionally, patients who were not narcotic naive were prescribed oxycontin 10 mg PO twice daily. 

Duration

2012 - 2017

Outcome Measures

Postoperative visual analogue scale (VAS) scores for back pain; inpatient opioid use (converted to oral morphine-equivalents); total hospital length of stay; perioperative complications 

Baseline Characteristics

Group L (n= 90)

Group C (n= 69)

Age, years

Female

Revision surgery

VAS-Back pain

Charlson Comorbidity Index

Opioid naive

Surgical diagnosis

Adult scoliosis

Degenerative scoliosis

Kyphosis

Kyphoscoliosis

13%

31%

21%

34%

3%

36%

26%

35%

Osteotomy (3-column)

Bilateral iliac screw

Number of levels fused

Results

Endpoint

Group L (n= 90)

Group C (n= 69)

p-Value

Postoperative pain scores (postoperative day 1)

4.8

5.7

0.02

Postoperative opioid utilization, total morphine-equivalents

Hospital length of stay, days

Group L appeared to transition off intravenous (IV) narcotics significantly faster: 52.6% less IV use by postoperative day 3 compared with control arm (12 vs. 25.4 mg, p= 0.03); no other statistically significant differences at any time point in opioid consumption between groups 

Linear regression analysis showed no difference between the trends in pain scores between the two cohorts; other than postoperative day 1, no further differences in pain scores were seen between the two groups 

No differences in overall postoperative complication rates 

NS, not significant

Adverse Events

N/A

Study Author Conclusions

The use of LB in adult spinal deformity surgery does not appear to provide clinically important improvements in postoperative pain at the manufacturer's recommended dosage. Furthermore, while patients receiving LB may transition more quickly off of IV narcotics, this does not appear to translate to an overall decrease in narcotic consumption, hasten return of bowel function, or decrease hospital lengths of stay. Future prospective randomized control trials are warranted. The use of varying dosages of LB may also help further clarify the true efficacy of LB in the setting of spinal deformity surgery. 

InpharmD Researcher Critique

The retrospective nature of the study limits the ability to control for confounding variables, potentially affecting the overall validity of the results. This was also a single center study, limiting the overall generalizability of the results. 

Retrospective Assessment of the Use of Liposomal Bupivacaine in Lumbar Fusions in Immediate Postoperative Hospital Care

Design

Retrospective cohort study

N= 122

Objective

To determine the effects of liposomal bupivacaine (LB) in patients undergoing posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF)

Study Groups

LB (n= 97)

Control (n= 25)

Inclusion Criteria

Age ≥ 18 years, underwent either an elective PLIF or TLIF for degenerative changes

Exclusion Criteria

Pregnant, experienced prolonged sedation secondary to intubation (i.e., intubation lasting > 6 hours postoperatively), had an allergy to amide local anesthetics, received pain management using a patient-controlled or nurse-controlled analgesia pump postoperatively, or if they were admitted for a trauma-related injury

Methods

Patient data were compiled retrospectively and compared with a historical cohort of consecutive patients not receiving LB. Both groups received 10 mL of lidocaine or bupivacaine hydrochloride with epinephrine at the skin surface before skin incision for bleeding control. However, in the experimental group, patients were given an additional 266 mg (20 mL) of LB injection mixed with 150 mg (20 mL) bupivacaine hydrochloride in a 1:1 ratio for a total 40 mL. 

Duration

Patients underwent surgery between March 2014 and November 2016

Outcome Measures

Primary: postoperative opioid use

Secondary: postoperative pain scores (per visual analog scale [VAS]), hospital length of stay (LOS)

Baseline Characteristics

LB (n= 97)

Control (n= 25)

Age, years

Female

Surgical procedure

PLIF

TLIF

PLIF + TLIF

94%

3%

3%

76%

12%

12%

Number of levels fused

1

2

≥ 3

76%

17%

7%

60%

20%

20%

Results

Endpoint

LB 

Control

p-Value

Total opioid use, MME

0-12 hours

12-24 hours

24-36 hours

36-48 hours

48-60 hours*

60-72 hours

17.6 ± 14.2 (n= 97)

12.5 ± 10 (n= 97)

10.4 ± 11 (n= 79)

10.8 ± 9.7 (n= 62)

6.8 ± 7.3 (n= 44)

9.6 ± 8.6 (n= 26) 

16.2 ± 14.3 (n= 25)

11.7 ± 12.6 (n= 24)

12.7 ± 15.2 (n= 23)

13.6 ± 13.7 (n= 20)

11.1 ± 14.2 (n= 20)

12.8 ± 13.4 (n= 14)

NS

NS

NS

NS

NS

NS

Pain score, VAS

0-12 hours

12-24 hours

24-36 hours

36-48 hours

48-60 hours

60-72 hours

5.2 ± 2.1

4.3 ± 2.5

3.4 ± 3

3.2 ± 3

1.8 ± 2.8

2.7 ± 3.1 

3.9 ± 2.6

3.4 ± 2.3

2.7 ± 2.9

3.2 ± 3.3

2.4 ± 3.4

2.6 ± 3.3

0.0079

NS

NS

NS

NS

NS 

LOS, days

1.94

3.08

0.0043

*At 48-60 hours, when assessing IV opioid use only and not oral opioid use, a significant difference was noted between LB and control group (0.3 ± 1.3 vs. 1.2 ± 2.6; p= 0.0494).

MME, morphine milligram equivalents; NS, not significant

Adverse Events

Study Author Conclusions

The use of LB was found to have no significant effect on postoperative opioid use after a PLIF or TLIF surgical procedure in this retrospective study with a control group. Patients were found to have similar pain scores between groups at all time points except 0—12 hours. However, patients were discharged from the hospital earlier in the LB group. Additional prospective studies are warranted to assess the use of LB in a more controlled environment.

InpharmD Researcher Critique

This study is subject to inherent limitations of a retrospective analysis. Overall, a limited sample size was included, and total number of patients was unbalanced between groups. More patients in the LB group underwent single-level surgery, which may result in less pain and decreased opioid need. 

Intramuscular Liposomal Bupivacaine Decreases Length of Stay and Opioid Usage Following Lumbar Spinal Fusion

Design

Retrospective cohort review

N= 210

Objective

To investigate the efficacy of liposomal bupivacaine (LB) in patients undergoing lumbar spinal fusion 

Study Groups

LB (n= 105)

Non-LB formulation (n= 105)

Inclusion Criteria

Underwent posterior lumbar spinal fusion surgery; received LB or non-LB formulation

Exclusion Criteria

N/A

Methods

A propensity score-based matching algorithm was utilized to match patients who received LB with the historical cohort of patients who received non-LB formulations. 

Preoperative pain management included a single oral dose of acetaminophen 975 mg PO or rectally and gabapentin 900 mg or pregabalin 75 mg (unless taking a different dose before admission). Prior to incision, bupivacaine 0.25% with epinephrine was injected into the skin and at the end of each surgery all patients received a single intrathecal injection of fentanyl 25 mcg using a 30 G needle through an intact interlaminar space. Total intravenous anesthesia using remifentanil and propofol was used for all surgeries. 

The LB-saline mixture was prepared using 20 mL of LB mixed with 100 mL of normal saline; this was injected using a 20 G needle into the paraspinal muscles bilaterally prior to wound closure with 60 mL injection on either side of the midline incision. Syringes were aspirated before injecting to prevent intravascular injection; 4-5 depot injections were distributed evenly throughout the deep and superficial muscle tissue. LB was not injected into the skin or subcutaneous tissue. 

Duration

April 2015 - September 2016

Outcome Measures

Postoperative opioid consumption (morphine milligram equivalent), pain scores (using a visual analog scale), length of stay (LOS), cost

Baseline Characteristics

LB (n= 105)

Non-LB formulation (n= 105)

Age, years

Male

Black

Charlson Comorbidity Index

Results

Endpoint

LB (n= 105)

Non-LB formulation (n= 105)

p-Value

Cumulative pain scores

Activity

Rest

4.8 ± 1.5

3.8 ± 1.2

4.7 ± 1.5

3.5 ± 1.4

0.5

0.1

Opioid use (geometric mean [95% CI])

Day of surgery

Postoperative day 1

Postoperative day 2

102.7 (90.6 to 116.4)

49 (41.2 to 58.3)

29.6 (22 to 39.8)

152.1 (129.4 to 178.9)

81.4 (66.3 to 99.9)

48.7 (38.7 to 61.3)

< 0.001

Time to ambulation

≤ 12 h

12-24 h

> 24 h

61.2%

33%

5.8%

3%

90%

7%

< 0.001

< 0.001

0.73

Days to discharge

Postoperative day 1

Postoperative day 2

Postoperative day 3

Postoperative day 4

32.4%

56.2%

7.6%

3.8%

1%

37.1%

51.4%

10.5%

< 0.001

0.006

< 0.001

0.06

Total direct cost

Total pharmaceutical cost

$17,424.97 ± 4,866.14

$676.23 ± 117.70

$20,752.13 ± 7,749.33

$486.58 ± 194.15

< 0.001

N/A

CI= confidence interval 

Adverse Events

N/A

Study Author Conclusions

Adjunctive usage of LB with lumbar fusion surgeries promotes earlier mobility, lower opioid consumption, and shorter length of stay resulting in overall lower health care cost. 

InpharmD Researcher Critique

This study is limited by its retrospective design, however the using of propensity matching may help to minimize potential confounding variables. Of note, intramuscular use is an off-label route of administration and the results may not be able to be extrapolated to approved administration methods. 

The Role of Liposomal Bupivacaine in Multimodal Pain Management following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis: Faster and Farther with Less Opioids

Design

Single-center, retrospective review

N= 119

Objective

To evaluate the effect of intraoperative liposomal bupivacaine (LB) infiltration on post-surgical pain management in adolescent idiopathic scoliosis (AIS) patients

Study Groups

LB (n= 53)

Control (n= 66)

Inclusion Criteria

Age < 18 years, underwent primary posterior spinal fusion (PSF)

Exclusion Criteria

Non-AIS spine conditions, fusion to the pelvis, revision procedures, growing rod instrumentation

Methods

All patients received a multimodal weight-based perioperative pain management regimen per standard protocol, consisting of preoperative gabapentin, acetaminophen, and celecoxib as well as postoperative gabapentin, clonidine, and ketorolac (which was then transitioned to naproxen on postoperative day 1). Additionally, patients in the LB group received regional analgesia with intraoperative local infiltration of LB 4 mg/kg (maximum dose 266 mg) as an erector spinae block (ESB) into the erector spinae muscles prior to muscle closure. Patients in control group received only standard multimodal pain management protocol. 

Duration

Underwent procedure between January 2021 and September 2022

Outcome Measures

Postoperative opioid consumption, postoperative pain scores (visual analog scale [VAS]), ambulation, length of stay (LOS)

Baseline Characteristics

LB (n= 53)

Control (n= 66)

Age, years

Female

Cobb angle, degrees

Number of levels fused

Results

Endpoint

LB (n= 53)

Control (n= 66)

p-Value

Postoperative opioid consumption

Oral morphine equivalents

Oral opioids only

44.5 ± 29

43 (81.1%)

70.2 ± 30.3

27 (40.9%)

< 0.001

0.001

Postoperative pain score, VAS

POD 0

POD 1

POD 2

4.78 ± 2.06

4.76 ± 1.69

4.76 ± 1.48

5.25 ± 1.8

5.30 ± 1.54

5.03 ± 1.54

0.216

0.072

0.326

Total ambulation distance

POD 1

POD 2

282.3 ± 317.9

888.7 ± 651.8

149.71 ± 143.6

553.4 ± 246.5

0.003

0.002

LOS, days

Discharged on POD 2

2.42 ± 0.61

54.7%

2.74 ± 0.58

27.3%

0.005

0.002

Adverse Events

Study Author Conclusions

This study confirmed the addition of intraoperative ESB with LB to the standard multimodal pain regimen demonstrated decreased total and IV opioid utilization to achieve the same degree of analgesia. The results suggest LB also is associated with decreased hospital LOS and greater mobility in terms of ambulation distance. Therefore, the use of a multimodal approach to pain management that includes LB is effective in opioid limitation and avoidance while improving ambulation postoperatively and decreasing LOS. 

InpharmD Researcher Critique

This small retrospective study is subject to inherent limitations of its study design and sample size, as well as being restricted to a single institution.